{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:06:06Z","timestamp":1789445166982,"version":"build-2803163510"},"reference-count":38,"publisher":"Cold Spring Harbor Laboratory","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>\n                    \u03b2-Mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme \u03b2-mannosidase. The disease is caused by mutations in\n                    <jats:italic>MANBA<\/jats:italic>\n                    and is extremely rare in humans. Although the clinical presentation is heterogeneous, common symptoms include various degrees of developmental delay, behavioral disturbances, hearing loss, and frequent infections. We report a 15-yr-old girl presenting with mild intellectual disability, sensorineural hearing loss, severe behavioral disturbances, dysmorphic traits, and evolving angiokeratomas. Copy-number variation analysis of next-generation sequencing (NGS) data indicated increased coverage in exons 8\u201311 of\n                    <jats:italic>MANBA<\/jats:italic>\n                    . Low \u03b2-mannosidase activity (1 \u00b5katal\/kg protein, refv 25\u201340) established the diagnosis of \u03b2-mannosidosis. Whole-genome sequencing (WGS) and cDNA analysis revealed a novel homozygous intragenic inverted duplication in\n                    <jats:italic>MANBA,<\/jats:italic>\n                    where a 13.1-kb region between introns 7 and 11 was duplicated and inserted in an inverted orientation, creating a 67-base nonduplicated gap at the insertion point. Both junctions showed microhomology regions. The inverted duplication resulted in exon skipping of exons 8\u20139 or 8\u201310. Our report highlights the importance of copy-number variation analysis of data from NGS and in particular the power of WGS in the identification and characterization of copy-number variants.\n                  <\/jats:p>","DOI":"10.1101\/mcs.a003954","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T20:39:30Z","timestamp":1552941570000},"page":"a003954","source":"Crossref","is-referenced-by-count":27,"title":["\u03b2-Mannosidosis caused by a novel homozygous intragenic inverted duplication in\n                    <i>MANBA<\/i>"],"prefix":"10.1101","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-0983","authenticated-orcid":false,"given":"Maria","family":"Blomqvist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Falkenberg","family":"Smeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Lindgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Sikora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde Monica Frostad","family":"Riise Stensland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Asin-Cayuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"key":"2021112506182645000_5.3.a003954.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.1.75"},{"key":"2021112506182645000_5.3.a003954.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00172-5"},{"key":"2021112506182645000_5.3.a003954.3","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-10-38"},{"key":"2021112506182645000_5.3.a003954.4","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2013_227"},{"key":"2021112506182645000_5.3.a003954.5","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.25"},{"key":"2021112506182645000_5.3.a003954.6","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv710"},{"key":"2021112506182645000_5.3.a003954.7","doi-asserted-by":"publisher","DOI":"10.5144\/0256-4947.2004.393"},{"key":"2021112506182645000_5.3.a003954.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198611063151918"},{"key":"2021112506182645000_5.3.a003954.9","doi-asserted-by":"publisher","DOI":"10.1007\/BF01800054"},{"key":"2021112506182645000_5.3.a003954.10","doi-asserted-by":"publisher","DOI":"10.1007\/BF01804383"},{"key":"2021112506182645000_5.3.a003954.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-41018-40122-41436"},{"key":"2021112506182645000_5.3.a003954.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.07.001"},{"key":"2021112506182645000_5.3.a003954.13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-S3-S22"},{"key":"2021112506182645000_5.3.a003954.14","doi-asserted-by":"crossref","first-page":"5185","DOI":"10.1016\/S0021-9258(19)69384-1","article-title":"Caprine \u03b2-mannosidosis. 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